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Cytoskeleton organization and dynamics in stem cells and neurons of patients with autism spectrum disorders

Grant number: 12/50100-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2012
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Maria Rita dos Santos e Passos Bueno
Grantee:Karina Griesi Oliveira
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Autism spectrum disorders (ASD) are characterized by deficits in reciprocal social interaction and communication as well as the presence of repetitive behaviors. ASD are genetically heterogeneous, which has been made difficult the development of molecular tests for diagnosis and the understanding of their etiology. On the other hand, it is interesting to note that several genes implicated in the etiology of ASD are part of common molecular pathways or mechanisms, indicating that these different genetic alterations may cause simmilar effects during neurogenesis, leading to the same behavioral features. An example of that is the mechanisms involved in cytoskeleton dinamics regulation, which are essential for organization and plasticity of dendritic spines as well as axonal growth and guidance. However, the relationship between these mechanisms and the etiology of ASD has been poorly explored in the literature, specially in their functional aspects. Reprogramming of somatic cells to a pluripotent state by transient over-expression of specific factors has allowed for the development of neuronal célis of genomes that are pre-disposed to human diseases, which represents excellent models for functional studies of ASD etiology. Thus, our main aim in this project is to study the mechanisms of cytoskeleton dinamics regulation in cells from ASD idiopathic patients. As a first model for initial screening, we will make use of dental pulp stem cells from these patients, and, subsequently, neuronal models obtained from reprogrammed cells. We believe that this project can contribute for the understanding of the common molecular mechanisms involved in ASD etiology as well as for the finding of new drugs that can help in the treatment of these patients. (AU)

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